Biochemical, clinical and neuroradiological (MRI) correlations in late-detected PKU patients

J Inherit Metab Dis. 1995;18(5):624-34. doi: 10.1007/BF02436009.


Brain magnetic resonance imaging (MRI) was performed in 17 late-detected PKU patients (aged 2.8-25 years). Twelve subjects had been treated late (0.7-4.5 years), and 5 not at all. Four were still on diet when the study was performed. Mental development was normal in 4 subjects, mildly retarded in 6, and moderately or severely retarded in 7. None had exhibited mental or neurological deterioration. On MRI examination a symmetrical increase of T2-weighted signal in the periventricular white matter was found in all patients, although to different degrees. Concomitant signal decrease on the T1-weighted sequences was detected in 9 patients. Ten subjects showed focal white-matter abnormalities. A variable degree of cortical and subcortical atrophy was found in 12 subjects, and asymmetry of lateral ventricles in 4. White-matter involvement correlated with phenylalanine concentrations during the year preceding (rs = 0.5706; p < 0.02) and at the time of (rs = 0.6182, p < 0.01) the investigation. Cortical and subcortical atrophy correlated with the patient's age (rs = 0.5889, p < 0.02, and rs = 0.5929, p < 0.02, respectively). We conclude that late-detected PKU patients showed the same MRI abnormalities reported in early-treated subjects and in subjects who underwent neurological deterioration; white-matter abnormalities possibly result from the recent exposure to high phenylalanine concentrations; in late-detected PKU subjects cerebral atrophy could be the late result of chronic exposure to high phenylalanine concentrations.

MeSH terms

  • Adolescent
  • Adult
  • Atrophy
  • Brain / metabolism
  • Brain / pathology*
  • Cerebral Cortex / pathology
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Phenylalanine / metabolism*
  • Phenylketonurias / diet therapy
  • Phenylketonurias / metabolism*
  • Phenylketonurias / pathology*


  • Phenylalanine